scholarly journals SAT-576 Possible Involvement of Thyroid Function in PCSK9 Inhibitor Therapy

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Masayasu Iwabuchi

Abstract INTRODUCTION Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition is an effective strategy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol lowering ability of statins. PCSK9, a serine protease that binds to the LDL receptor promoting its degradation, is an important regulator of LDL metabolism. In addition, LDL-cholesterol is also controlled by TSH and thyroid hormones via PCSK9. TSH has received increasing attention as being closely associated with increased LDL-cholesterol level and higher atherosclerotic risks. In vitro study, the effects of TSH on hepatic PCSK9 expression in HepG2 cells were reported (1). I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. This case highlights the involvement of thyroid function in PCSK9 Inhibitor therapy. CLINICAL CASE A 65-year-old man had a weight loss of 6 kg (13 lbs.) in 4 months, accompanied with fatigue. He had a past history of myocardial infarction and his LDL was 83 mg/dL by 2.5mg of rosuvastatin and heart rate was controlled by 10mg of carvedilol. Six months ago, he started a PCSK9 Inhibitor therapy with 140mg of evolocumab every 2 weeks for 6 weeks. He had no preceding viral illness and denied anterior neck pain or tenderness. His height was 1.53 m, weight 52.6 kg (115 lbs.), and body mass index (BMI) 22.46 kg/m2. His thyroid was not enlarged and non-tender without clear palpable thyroid nodules or neck lymph nodes. Hyperthyroidism was suspected and confirmed by thyroid function tests: TSH was less than 0.0005 μIU/mL (normal 0.35–4.94), and free T4 1.830 ng/dL (0.70–1.48). Graves’ disease was considered, and thyroid antibody tests performed. Thyroid peroxidase (TPO) antibody titer was less than 9 IU/mL (<9), and TSI 141% (<120%). To confirm the diagnosis of this hyperthyroid patient, Technetium-99m uptake and scan was done which showed uptake of 0.8% (0.5–7%). After careful observation for 2 months with 5mg of carvedilol, he turned asymptomatic and free T4 lowered to 1.480 ng/dL and TSH remained less than 0.0005 μIU/mL. CLINICAL LESSONS I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. There has been no report of hyperthyroidism induced by PCSK9 inhibitors. Immunological influence of anti-PCSK9 therapy on thyroid is unknown. In this case, the decrease of TSH due to hyperthyroidism was considered to reduce hepatic PCSK9 expression, leading to additive effect to PCSK9 inhibitor. PCSK9 inhibitors may modify the effects of hyperlipidemia treatment by causing changes in thyroid function. When using PCSK9 inhibitors, follow-up of thyroid function should be considered. This case highlights the involvement of thyroid function in PCSK9 inhibitor therapy. Reference (1) Gong, Y., Ma, Y., et al. Thyroid stimulating hormone exhibits the impact on LDLR/LDL-c via up-regulating hepatic PCSK9 expression. Metabolism. 2017;76;32–41

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A940-A941
Author(s):  
Nyembezi Dhliwayo ◽  
Rana Wajahat ◽  
Andriy Havrylyan ◽  
Alvia Moid ◽  
Walid Khayr ◽  
...  

Abstract There is considerable evidence that some Borrelial (Lyme spirochetal) proteins share significant antigenic properties with several thyroid-related proteins (e.g. TSH receptor, thyroglobulin, thyroid peroxidase) and can induce thyroid autoimmunity, sometimes associated with Hashimoto’s thyroiditis and perhaps also a “destructive thyroiditis” such as “silent” thyroiditis or “Hashitoxicosis.” As an acute illness, Lyme disease may also constitute a “non-thyroidal illness” capable of perturbing thyroid function tests without causing thyroid dysfunction. We report a 22-year old woman admitted with an acute paranoid schizophrenia, thyroid function tests consistent with autoimmunity, transient thyrotoxicosis (tachycardia, lid-lag, brisk DTR’s) and a greatly reduced radioiodine uptake. The thyroid was not palpably enlarged, nodular or tender. On screening assay, reactivity was demonstrated to 4 of 13 Borrelial proteins. Anti-Lyme IgM but not IgG, antibodies, were positive. This was consistent with recent Lyme disease infection. Serum TSH (NL: 0.358-3.74 mcU/ml), Free T4 (NL: 0.76-1.46 ng/dl), and Free T3 (NL: 2.18-3.98 pg/ml) were, respectively: Day1: 0.087 mcU/ml (suppressed), 1.52 ng/dl (slightly elevated), 2.07 pg/ml (slightly reduced); Day2: 0.148 (suppressed), 1.18 (normal), no FT3; Day4: 0.827 (normal), no FT4 or FT3; Day5: 1.66 (normal), 0.89 (normal), 1.77 (low). Anti-Tg and Anti-Peroxidase antibodies were both moderately elevated. Thyroid Stimulating Immunoglobulins were not elevated. The radioactive iodine uptake on Day4 was 2.8% (NL: 15-30% at 24 hr). Thyroid ultrasonogram was normal. An attractive explanation is that Lyme disease triggered a “destructive thyroiditis,” perhaps but not necessarily mediated by thyroid autoimmunity. This would account for the brief interval of thyrotoxicosis accompanied by a very low radioiodine uptake. Alternatively, Lyme disease, as an acute process, would expectedly be capable of eliciting the thyroid function abnormalities of “non-thyroidal illnesses” in general, as would acute psychosis, well-known to often resemble Graves’ disease at admission.


2016 ◽  
Vol 64 (4) ◽  
pp. 931.2-932
Author(s):  
P Shah ◽  
CJ Glueck ◽  
N Goldenberg ◽  
V Jetty ◽  
A Kumar ◽  
...  

BackgroundLDL cholesterol (LDLC) lowering has been revolutionized by PCSK9 inhibitors, Alirocumab (Praluent) and Evolocumab (Repatha), which have approved indications as an adjunct to diet-maximally tolerated cholesterol lowering therapy in heterozygous (HeFH) or homozygous (HoFH) familial hypercholesterolemia, and/or clinical atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient despite maximal tolerated therapy.MethodsWe applied FDA approved and commercial insurance eligibility criteria for PCSK9 inhibitor use in 734 patients serially referred over 3 years who then received ≥2 months maximally tolerated LDLC lowering diet-drug therapy with follow up LDLC ≥70 mg/dl, as well as in 37 patients approved by commercial insurance for PCSK9 inhibitors. We obtained estimates of the percentage of patients with HeFH and/or CVD who meet FDA and commercial insurance eligibility for PCSK9 inhibitors using LDLC goal-based guidelines.ResultsOf the 734 patients with LDLC ≥70 mg/dl after ≥2 months maximally tolerated LDLC lowering therapy, 220 (30%) had HeFH and/or CVD events with LDLC >100 mg/dl, meeting both FDA and commercial insurance criteria for PCSK9 inhibitor therapy. Sixty-six (9%) patients were statin intolerant, without HeFH or CVD events. Of the 37 patients whose PCSK9 inhibitor therapy was approved for coverage by medical insurance carriers, 34 (92%) had LDLC>100 mg/dl after ≥2 months on maximally tolerated LDLC lowering therapy. Sixteen (43%) of these 37 patients had HeFH without CVD (LDLC on maximally tolerated conventional treatment 181±48 mg/dl), 11 (30%) had CVD without HeFH (LDLC on maximally tolerated conventional treatment 122±22 mg/dl), and 8 (22%) had both HeFH and CVD (LDLC on maximally tolerated conventional treatment 204±56 mg/dl).ConclusionOf the 734 patients referred for high LDLC treatment, with LDLC ≥70 mg/dl after ≥2 months on maximally tolerated therapy, 220 (30%) had HeFH and/or CVD with LDLC >100 mg/dl, meeting both FDA and insurance criteria for PCSK9 inhibitor therapy. If 30% of patients with high LDLC and HeFH-CVD are eligible for PCSK9 inhibitors, then specialty pharmaceutical pricing models (∼$14,300/year) will collide with an estimated 16–21 million HeFH-CVD patients. Although the costs for PCSK9 inhibitors given to an estimated 16 to 21 million patients are extraordinary ($228–300 billion), we speculate that, when weighed against direct and indirect costs of CVD, on balance, the cost to society might be either none, or that society would, in fact, save money by an anticipated 50% reduction of CVD events with PCSK9 inhibitors. Whether the health care savings arising from the anticipated reduction of CVD on the PCSK9 inhibitors justify the broad population use of these agents remains to be determined.


2021 ◽  
Vol 12 ◽  
Author(s):  
David Tak Wai Lui ◽  
Ivan Fan Ngai Hung ◽  
Chi Ho Lee ◽  
Alan Chun Hong Lee ◽  
Anthony Raymond Tam ◽  
...  

BackgroundSome studies have indicated that interferon (IFN) may be valuable in COVID-19. We aimed to evaluate the impact of short-term IFN on incident thyroid dysfunction and autoimmunity among COVID-19 survivors.MethodsWe included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to January 2021 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured both on admission and at three months.Results226 patients were included (median age 55.0 years; 49.6% men): 135 were IFN-treated. There tended to be more abnormal TFTs upon reassessment in IFN-treated patients (8.1% vs 2.2%, p=0.080). 179 patients (65.4% IFN-treated) had a complete reassessment of anti-thyroid antibodies. There were significant increases in titres of both anti-thyroid peroxidase antibodies (anti-TPO: baseline 29.21 units [IQR: 14.97 – 67.14] vs reassessment 34.30 units [IQR: 18.82 – 94.65], p<0.001) and anti-thyroglobulin antibodies (anti-Tg: baseline 8.23 units [IQR: 5.40 – 18.44] vs reassessment 9.14 units [IQR: 6.83 – 17.17], p=0.001) in the IFN-treated group but not IFN-naïve group. IFN treatment (standardised beta 0.245, p=0.001) was independently associated with changes in anti-TPO titre. Of the 143 patients negative for anti-TPO at baseline, 8 became anti-TPO positive upon reassessment (seven IFN-treated; one IFN-naïve). Incident anti-TPO positivity was more likely to be associated with abnormal TFTs upon reassessment (phi 0.188, p=0.025).ConclusionIFN for COVID-19 was associated with modest increases in anti-thyroid antibody titres, and a trend of more incident anti-TPO positivity and abnormal TFTs during convalescence. Our findings suggest that clinicians monitor the thyroid function and anti-thyroid antibodies among IFN-treated COVID-19 survivors, and call for further follow-up studies regarding the clinical significance of these changes.


2019 ◽  
Vol 38 (1) ◽  
pp. 22-32 ◽  
Author(s):  
Najdana Gligorovic Barhanovic ◽  
Tanja Antunovic ◽  
Sreten Kavaric ◽  
Aleksandar Djogo ◽  
Vesna Kalimanovska Spasojevic

Summary Background: Laboratory thyroid function tests play a central role in the diagnosis of thyroid disorders. The aim of our cross-sectional study was to determine reference values for thyroid tests in a rigorously selected group of Montenegrin females, investigate the impact of possible age-related changes and the influence of the interassay bias between three frequently used immunoassays. Methods: Female subjects were randomly selected, aged between 20 and 69 and 946 of them met the selection criteria. TSH, fT3, fT4, thyroid peroxidase and thyroglobulin antibodies were measured. Eighty samples were further analyzed on two other immunochemistry platforms. Results: Median TSH progressively increased with age, there was no difference in fT3, while fT4 was significantly higher in the two oldest groups compared to the others. When using the age-related 97.5 percentile of TSH the percentage of reclassification was highest in the 20–29 years of age group (5.2%, p<0.05). In the oldest band, 7.7% had TSH values above cohort-specific and below the age-related upper reference limit. Bland-Altman bias plots revealed the highest interassay absolute mean difference between compared TSH assays of 24.5% and for fT4 assays of 13.8%. Conclusions: The correlation coefficients between fT3 assays from different manufacturers were low. Serum TSH and fT4 concentrations increased with age and the implementation of age-specific TSH reference intervals would be of interest. The bias between the three commercial immunoassays indicated that the standardization of thyroid function tests is a task of great importance.


2021 ◽  
Vol 10 (11) ◽  
pp. 2504
Author(s):  
Elena Izkhakov ◽  
Yacov Shacham ◽  
Merav Serebro ◽  
Iris Yaish ◽  
Yonit Marcus ◽  
...  

Elevated low-density lipoprotein (LDL) cholesterol is one of the leading causes of cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce LDL cholesterol levels with subsequent reductions in cardiovascular morbidity. Elevated aldosterone levels are also associated with a greater risk of cardiovascular morbidity. There are currently no published data on the impact of PCSK9 inhibitor monotherapy on the secretion of aldosterone. The aim of this study was to examine the effect of monotherapy with the PSCK9 inhibitor evolocumab on the lipid profile and aldosterone secretion level in high-risk cardiovascular patients. Lipid profile, sodium, potassium, aldosterone, cortisol, plasma renin activity, and adrenocorticotropic hormone (ACTH) levels were analyzed at baseline and after 3 months of evolocumab therapy. Each participant underwent a 250 mcg ACTH stimulation test upon study entry. Eight women and seven men were included in the study. Their median total cholesterol, LDL cholesterol, lipoprotein (a), apolipoprotein B100, and baseline and stimulated aldosterone levels were significantly lower after 3 months of evolocumab therapy. These heretofore unreported findings indicate that reductions in unstimulated and stimulated aldosterone secretion under evolocumab therapy could be associated with reductions in cardiovascular events, a possibility that warrants further investigation.


2020 ◽  
Vol 125 (1) ◽  
pp. 71-78
Author(s):  
Victor Pop ◽  
Johannes Krabbe ◽  
Wolfgang Maret ◽  
Margaret Rayman

AbstractThe present study reports on first-trimester reference ranges of plasma mineral Se/Zn/Cu concentration in relation to free thyroxine (FT4), thyrotropin (TSH) and thyroid peroxidase antibodies (TPO-Ab), assessed at 12 weeks’ gestation in 2041 pregnant women, including 544 women not taking supplements containing Se/Zn/Cu. The reference range (2·5th–97·5th percentiles) in these 544 women was 0·72–1·25 µmol/l for Se, 17·15–35·98 µmol/l for Cu and 9·57–16·41 µmol/l for Zn. These women had significantly lower mean plasma Se concentration (0·94 (sd 0·12) µmol/l) than those (n 1479) taking Se/Zn/Cu supplements (1·03 (sd 0·14) µmol/l; P < 0·001), while the mean Cu (26·25 µmol/l) and Zn (12·55 µmol/l) concentrations were almost identical in these sub-groups. Women with hypothyroxinaemia (FT4 below reference range with normal TSH) had significantly lower plasma Zn concentrations than euthyroid women. After adjusting for covariates including supplement intake, plasma Se (negatively), Zn and Cu (positively) concentrations were significantly related to logFT4; Se and Cu (but not Zn) were positively and significantly related to logTSH. Women taking additional Se/Zn/Cu supplements were 1·46 (95 % CI 1·09, 2·04) times less likely to have elevated titres of TPO-Ab at 12 weeks of gestation. We conclude that first-trimester Se reference ranges are influenced by Se-supplement intake, while Cu and Zn ranges are not. Plasma mineral Se/Zn/Cu concentrations are associated with thyroid FT4 and TSH concentrations. Se/Zn/Cu supplement intake affects TPO-Ab status. Future research should focus on the impact of trace mineral status during gestation on thyroid function.


Author(s):  
Shivani Patel ◽  
Venessa Chin ◽  
Jerry R Greenfield

Summary Durvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes is a rare immune-related adverse effect associated with the use of immune checkpoint inhibitor therapy. It is now being increasingly described reflecting the wider use of immune checkpoint inhibitor therapy. We report the case of a 49-year-old female who presented with polyuria, polydipsia and weight loss, 3 months following the commencement of durvalumab. On admission, she was in severe diabetic ketoacidosis with venous glucose: 20.1 mmol/L, pH: 7.14, bicarbonate 11.2 mmol/L and serum beta hydroxybutyrate: >8.0 mmol/L. She had no personal or family history of diabetes or autoimmune disease. Her HbA1c was 7.8% and her glutamic acid decarboxylase (GAD) antibodies were mildly elevated at 2.2 mU/L (reference range: <2 mU/L) with negative zinc transporter 8 (ZnT8) and islet cell (ICA) antibodies. Her fasting C-peptide was low at 86 pmol/L (reference range: 200–1200) with a corresponding serum glucose of 21.9 mmol/L. She was promptly stabilised with an insulin infusion in intensive care and discharged on basal bolus insulin. Durvalumab was recommenced once her glycaemic control had stabilised. Thyroid function tests at the time of admission were within normal limits with negative thyroid autoantibodies. Four weeks post discharge, repeat thyroid function tests revealed hypothyroidism, with an elevated thyroid-stimulating hormone (TSH) at 6.39 mIU/L (reference range: 0.40–4.80) and low free T4: 5.9 pmol/L (reference range: 8.0–16.0). These findings persisted with repeat testing despite an absence of clinical symptoms. Treatment with levothyroxine was commenced after excluding adrenal insufficiency (early morning cortisol: 339 nmol/L) and hypophysitis (normal pituitary on MRI). Learning points: Durvalumab use is rarely associated with fulminant autoimmune diabetes, presenting with severe DKA. Multiple endocrinopathies can co-exist with the use of a single immune checkpoint inhibitors; thus, patients should be regularly monitored. Regular blood glucose levels should be performed on routine pathology on all patients on immune checkpoint inhibitor. Clinician awareness of immunotherapy-related diabetes needs to increase in an attempt to detect hyperglycaemia early and prevent DKA.


Author(s):  
Vasim Ismail Patel ◽  
Akshay B. K.

<p class="abstract"><strong>Background:</strong> The thyroid is an<strong> </strong>endocrine gland. It secretes two hormones thyroxine (T<sub>4</sub>), triiodothyronine (T<sub>3</sub>). Hypothyroidism is a common condition encountered by a clinician. Subclinical hypothyroidism (SCH) defined as normal free thyroxine (T4) and elevated thyroid stimulating hormone (TSH), is primarily a biochemical diagnosis with or without clinical symptoms. Studies have observed that TSH levels vary at different times in a day. In practice not much importance is given to the timing of the sample collection (pre-prandial or post-prandial sate). SCH is diagnosed depending on TSH value. So the condition may be under or over diagnosed based on a single value. So we conducted this study to determine whether timing of sample collection had any significant relationship in the determination of levels of thyroid hormones.</p><p class="abstract"><strong>Methods:</strong> The study was carried on 114 patients who visited ENT department, NMCH between July 2018 and June 2019. Group-1 consisted of 38 normal patients. Group-2 consisted of 36 hypothyroidism patients GROUP-3 consisted of 40 subclinical hypothyroidism patients. Thyroid function tests (TSH and free T4) were done in fasting state and 2 hours postprandially.  </p><p class="abstract"><strong>Results:</strong> TSH values were found to be significantly lowered after food in all the three groups. Free T4 values did not show any statistically significant alteration after food.</p><p class="abstract"><strong>Conclusions:</strong> There was a significant decline in TSH values postprandially. This might lead to inappropriate diagnosis and management of patients as cases of hypothyroidism, especially in cases of sub clinical hypothyroidism.</p>


2021 ◽  
Vol 14 (4) ◽  
pp. e240924
Author(s):  
Preethi Padmanaban ◽  
Eric Nylen ◽  
Kenneth Burman ◽  
Sabyasachi Sen

We report a case of 34-year-old clinically asymptomatic woman who had been followed for 6 years for hyperthyroidism with thyroid stimulating hormone <0.006 uIU/mL, free T4 1.98 ng/mL, free T3 5.3 pg/mL, elevated thyroid stimulating immunoglobulin 1.70 IU/L, thyroid peroxidase antibody 38 IU/mL and thyroglobulin antibody 9.3 IU/mL. Radioiodine thyroid scan showed minimal uptake in both thyroid lobes (24-hour uptake was 0.3%). She subsequently underwent evaluation for lower abdominal pain and menstrual irregularities, which revealed a large left ovarian cyst measuring 15.9 cm × 10.8 cm × 13.2 cm and right-sided ovarian cyst measuring 2.7 cm × 3.3 cm × 3.5 cm. Laparoscopic bilateral ovarian cystectomy was performed and the final pathology revealed struma ovarii of the left ovarian cyst with the entire ovarian tumour made up of benign thyroid tissue. Thyroid function tests performed 3 months after surgical removal of struma ovarii showed euthyroidism. We present a rare case with detailed laboratory and immunological data before and after ovarian extirpation with resolution of hyperthyroidism associated with functional struma ovarii.


1987 ◽  
Vol 80 (12) ◽  
pp. 750-752 ◽  
Author(s):  
C Farror ◽  
M L Wellby ◽  
C Beng

Clinical and biochemical studies on a family in which 3 members have familial dysalbuminaemic hyperthyroxinaemia (FDH) are presented. They were clinically euthyroid with elevated serum thyroxine (T4) and free T4 indices but normal free T4 by equilibrium dialysis and normal serum triiodothyronine (total and free). All thyroid function tests on the remaining family members were normal. The inheritance is consistent with autosomal dominance. Also presented are data on 4 unrelated patients with FDH and two patients with T4 autoantibodies. The methods for detecting FDH, T4 antibodies and other causes of euthyroid hyperthyroxinaemia are now freely available. Since these anomalies may be more common than previously supposed, clinical awareness of the conditions is necessary to protect patients from the consequences of incorrect diagnosis of thyrotoxicosis.


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